Emrelis Drug Information

EMRELIS is indicated for the treatment of adult patients with locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression, as determined by an FDA-approved test, who have received a prior systemic therapy. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Patient Selection

Select patients for treatment with EMRELIS based on the presence of high c-Met protein overexpression in patients with non-squamous NSCLC. Information on FDA-approved tests for the detection of high c-Met protein overexpression is available at: http://www.fda.gov/CompanionDiagnostics.

Recommended Dosage

The recommended dosage of EMRELIS is 1.9 mg/kg (up to a maximum of 190 mg for patients greater than or equal to 100 kg) administered as an intravenous infusion over 30 minutes every 2 weeks until disease progression or unacceptable toxicity.

Dosage Modifications for Adverse Reactions

The recommended dose reductions for adverse reactions are provided in Table 1. Table 1. Recommended The recommended dosage modifications of EMRELIS for adverse reactions are provided in Table 2.

Table 2. EMRELIS Interstitial Lung Disease (ILD)/Pneumonitis 2. 4 Recommended Premedications for Patients Who Experience Infusion-Related Reactions Table 3 contains the recommended premedications for patients who experience infusion-related reactions to EMRELIS, for subsequent infusions. Table 3: Recommended Premedications for Patients Who Experience Infusion-Related Reactions 2. 5 Preparation and Administration EMRELIS contains a hazardous component.

Follow applicable special handling and disposal procedures in accordance with local requirements. 1 Reconstitute and further dilute EMRELIS prior to intravenous infusion. Reconstitution of Lyophilized EMRELIS Before reconstitution, allow the vial to reach room temperature after removal of the vial from storage condition. Calculate the recommended dose based on the patient’s weight to determine the number of vials needed.

For patients weighing greater than or equal to 100 kg, use 190 mg dose. More than one vial may be needed to achieve the calculated dose. Using a sterile syringe, slowly inject Sterile Water for Injection, using the volume provided in Table 4, into the EMRELIS vial containing the lyophilized powder, which has a whole or fragmented cake-like appearance.

The reconstituted solution has a concentration of 20 mg/mL EMRELIS. Table 4. Reconstitution Volumes Swirl the vial gently until completely dissolved.

Do not shake. Inspect the reconstituted solution for particulate matter and discoloration. The solution should appear clear to slightly opalescent and colorless to slightly yellow.

Discard the vial if the reconstituted solution is discolored, is cloudy, or contains visible particulates. Use reconstituted EMRELIS immediately. If not used immediately, store the reconstituted EMRELIS vials in a refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours from the time of reconstitution.

Do not freeze. Each vial of EMRELIS is intended for one-time use only. Discard any unused drug remaining in the vial.

Dilution in Infusion Bag Calculate the required dose volume (mL) of reconstituted EMRELIS solution based on the prescribed dose. Withdraw the calculated dose volume (mL) of reconstituted solution from the EMRELIS vial using a sterile syringe. Discard any unused portion remaining in the vial(s).

Inject the calculated amount of reconstituted solution into 0.9% Sodium Chloride Injection infusion bag so that the final EMRELIS concentration is between 1 mg/mL and 10 mg/mL. Use only 0.9% Sodium Chloride Injection. Gently invert the infusion bag to thoroughly mix the solution.

Do not shake. After preparing the dose for infusion, visually inspect the bag content for particulates and discard if present. If not used immediately, the diluted solution can be stored in a refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours and an additional 4 hours at room temperature at 9°C to 30°C (48°F to 86°F) until the end of administration.

Do not freeze. Method of Administration If the prepared infusion solution was stored refrigerated at 2°C to 8°C (36°F to 46°F), allow the solution to reach room temperature prior to administration. Administer by intravenous infusion over 30 minutes using a dedicated infusion line with a 0.20 or 0.22 micron in-line filter made of polyether sulfone (PES), polyvinylidene fluoride (PVDF), or Polyamide (PA).

Do not mix EMRELIS with other drugs or administer other drugs through the same intravenous line.

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. LUMINOSITY The safety population described in WARNINGS AND PRECAUTIONS and below reflects exposure to EMRELIS in 168 patients with locally advanced or metastatic EGFR wild-type non-squamous NSCLC with c-Met protein overexpression who received EMRELIS as a single agent administered at 1.9 mg/kg intravenously every 2 weeks in the LUMINOSITY study. Among patients who received EMRELIS, 42% were exposed for 6 months or longer and 11% were exposed for greater than one year.

Serious adverse reactions occurred in 35% of patients. Permanent discontinuations of EMRELIS due to adverse reactions occurred in 30% of patients. Adverse reactions which resulted in permanent discontinuation of EMRELIS in ≥2% included peripheral neuropathy and ILD/pneumonitis.

Dosage interruptions due to adverse reactions occurred in 44% of patients. Adverse reactions which required dosage interruption in ≥2% of patients included peripheral neuropathy, fatigue, pneumonia, increased ALT, blurred vision, COVID-19, ILD/pneumonitis, and keratitis. Dose reductions due to adverse reactions occurred in 28% of patients.

Adverse reactions which required dose reductions in ≥2% of patients included peripheral neuropathy, fatigue, and keratitis. The most common adverse reactions (≥20%) were peripheral neuropathy, fatigue, decreased appetite, and peripheral edema. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, increased glucose, increased ALT, increased gamma glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin and decreased calcium.

Table 5 summarizes the adverse reactions in LUMINOSITY. Table 5. Adverse Reactions (≥10%) in Patients with EGFR Wild-Type Non-squamous NSCLC with c-Met Protein Overexpression in LUMINOSITY Other clinically relevant adverse reactions in <10% of patients who received EMRELIS included arthralgia, dizziness, dry eye, infusion-related reaction and photophobia.

Table 6 presents laboratory abnormalities in LUMINOSITY. Table 6. Select Laboratory Abnormalities (≥10%) that Worsened from Baseline in Patients with EGFR Wild-Type Non-squamous NSCLC with c-Met Protein Overexpression in LUMINOSITY Percentages were calculated using patients with worsening laboratory values from baseline and the number of patients with both baseline and post-treatment measurements as the denominator.

Effect of Other Drugs on EMRELIS Strong CYP3A Inhibitors

Concomitant use with strong CYP3A inhibitors may increase unconjugated MMAE AUC, which may increase the risk of EMRELIS adverse reactions. Monitor patients for adverse reactions when EMRELIS is given concomitantly with strong CYP3A inhibitors.

Pregnancy Risk Summary Based on the mechanism of action and findings in animals, EMRELIS can cause fetal harm when administered to a pregnant woman. There are no available human data on EMRELIS use in pregnant women to inform a drug-associated risk. In an animal reproduction study, administration of the small molecule component of EMRELIS, MMAE, to pregnant rats during organogenesis resulted in embryo-fetal mortality and structural abnormalities at exposures similar to the clinical exposure at the recommended dose.

Advise patients of the potential risks to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Data Animal Data No embryo-fetal development studies in animals have been performed with telisotuzumab vedotin-tllv.

In an embryo-fetal development study in pregnant rats, administration of two intravenous doses of MMAE, the small molecule component of EMRELIS, on gestational days 6 and 13 caused embryo-fetal mortality and structural abnormalities, including protruding tongue, agnathia, malrotated limbs, and gastroschisis compared to controls at a dose of 0.2 mg/kg (approximately 2 times the human area under the curve at the recommended dose).

Pediatric Use Safety and effectiveness of EMRELIS have not been established in pediatric patients.